Background Information
Galactosemia is a disorder that affects how the body processes a simple sugar called galactose. A small amount of galactose is present in many foods. It is primarily part of a larger sugar called lactose, which is found in all dairy products and many baby formulas. The signs and symptoms of galactosemia result from an inability to use galactose to produce energy.
Several types of galactosemia have been identified. These conditions are each caused by mutations in a particular gene, and affect different enzymes involved in breaking down galactose. Classic galactosemia, also known as type I, is the most common and most severe form of the condition. Galactosemia type II (also called galactokinase deficiency) and type III (also called galactose epimerase deficiency) cause different patterns of signs and symptoms.
If infants with classic galactosemia are not treated promptly with a low-galactose diet, life-threatening complications appear within a few days after birth. Affected infants typically develop feeding difficulties, a lack of energy (lethargy), a failure to gain weight and grow as expected (failure to thrive), yellowing of the skin and whites of the eyes (jaundice), liver damage, and bleeding. Other serious complications of this condition can include overwhelming bacterial infections (sepsis) and shock. Affected children are also at increased risk of delayed development, clouding of the lens of the eye (cataract), speech difficulties, and intellectual disability. Females with classic galactosemia may experience reproductive problems caused by ovarian failure.
Galactosemia type II causes fewer medical problems than the classic type. Affected infants develop cataracts, but otherwise experience few long-term complications. The signs and symptoms of galactosemia type III vary from mild to severe and can include cataracts, delayed growth and development, intellectual disability, liver disease, and kidney problems.
Mutations in the
GALE
,
GALK1
, and
GALT
genes cause galactosemia.
The
GALE
,
GALK1
, and
GALT
genes provide instructions for making enzymes that are essential for processing galactose obtained from the diet. These enzymes break down galactose into another simple sugar, glucose, and other molecules that the body can store or use for energy.
Mutations in the
GALT
gene are responsible for classic galactosemia (type I). Most of these genetic changes almost completely eliminate the activity of the enzyme produced from the
GALT
gene, preventing the normal processing of galactose and resulting in the life-threatening signs and symptoms of this disorder. Another
GALT
gene mutation, known as the Duarte variant, reduces but does not eliminate the activity of the enzyme. People with the Duarte variant tend to have much milder features of galactosemia.
Galactosemia type II results from mutations in the
GALK1
gene, while mutations in the
GALE
gene underlie galactosemia type III (Epimerase Deficiency Galactosemia). Like the enzyme produced from the
GALT
gene, the enzymes made from the
GALK1
and
GALE
genes play important roles in processing galactose. A shortage of any of these critical enzymes allows galactose and related compounds to build up to toxic levels in the body. The accumulation of these substances damages tissues and organs, leading to the characteristic features of galactosemia.
Molecular genetic testing is available for
GALT
